crossing96/oncoscreening huggingface dataset:
Predicting muscle invasion in bladder cancer based on MRI: A comparison of radiomics, and single-task and multi-task deep learning.	BACKGROUND AND OBJECTIVES: Radiomics and deep learning are two popular technologies used to develop computer-aided detection and diagnosis schemes for analysing medical images. This study aimed to compare the effectiveness of radiomics, single-task deep learning (DL) and multi-task DL methods in predicting muscle-invasive bladder cancer (MIBC) status based on T2-weighted imaging (T2WI). METHODS: A total of 121 tumours (93 for training, from Centre 1; 28 for testing, from Centre 2) were included. MIBC was confirmed with pathological examination. A radiomics model, a single-task model, and a multi-task model based on T2WI were constructed in the training cohort with five-fold cross-validation, and validation was conducted in the external test cohort. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of each model. DeLong's test and a permutation test were used to compare the performance of the models. RESULTS: The area under the ROC curve (AUC) values of the radiomics, single-task and multi-task models in the training cohort were: 0.920, 0.933 and 0.932, respectively; and were 0.844, 0.884 and 0.932, respectively, in the test cohort. The multi-task model achieved better performance in the test cohort than did the other models. No statistically significant differences in AUC values and Kappa coefficients were observed between pairwise models, in either the training or test cohorts. According to the Grad-CAM feature visualization results, the multi-task model focused more on the diseased tissue area in some samples of the test cohort compared with the single-task model. CONCLUSIONS: The T2WI-based radiomics, single-task, and multi-task models all exhibited good diagnostic performance in preoperatively predicting MIBC, in which the multi-task model had the best diagnostic performance. Compared with the radiomics method, our multi-task DL method had the advantage of saving time and effort. Compared with the single-task DL method, our multi-task DL method had the advantage of being more lesion-focused and more reliable for clinical reference.	bladder
Comparison of sequential and joint nonlinear mixed effects modeling of tumor kinetics and survival following Durvalumab treatment in patients with metastatic urothelial carcinoma.	Standard endpoints such as objective response rate are usually poorly correlated with overall survival (OS) for treatment with immune checkpoint inhibitors. Longitudinal tumor size may serve as a more useful predictor of OS, and establishing a quantitative relationship between tumor kinetics (TK) and OS is a crucial step for successfully predicting OS based on limited tumor size measurements. This study aims to develop a population TK model in combination with a parametric survival model by sequential and joint modeling approaches to characterize durvalumab phase I/II data from patients with metastatic urothelial cancer, and to evaluate and compare the performance of the two modeling approaches in terms of parameter estimates, TK and survival predictions, and covariate identification. The tumor growth rate constant was estimated to be greater for patients with OS ≤ 16 weeks as compared to that for patients with OS > 16 weeks with the joint modeling approach (k(g)= 0.130 vs. 0.0551 week(-1), p-value < 0.0001), but similar for both groups (k(g) = 0.0624 vs.0.0563 week(-1), p-value = 0.37) with the sequential modeling approach. The predicted TK profiles by joint modeling appeared better aligned with clinical observations. Joint modeling also predicted OS more accurately than the sequential approach according to concordance index and Brier score. The sequential and joint modeling approaches were also compared using additional simulated datasets, and survival was predicted better by joint modeling in the case of a strong association between TK and OS. In conclusion, joint modeling enabled the establishment of a robust association between TK and OS and may represent a better choice for parametric survival analyses over the sequential approach.	bladder
Tumor Biomarkers for Bacillus Calmette-Guérin Response: What We Get Is Not What We Want.	Studies to date on biomarkers predictive of response to bacillus Calmette-Guérin (BCG) treatment for non-muscle-invasive bladder cancer have only identified markers with prognostic potential. There is an urgent need for larger study cohorts and for control arms comprising BCG-untreated patients to identify biomarkers with true ability to predict BCG response in classifying this patient population.	bladder
Frequent Telomerase Reverse Transcriptase Promoter and Fibroblast Growth Factor Receptor 3 Mutations Support the Precursor Nature of Papillary Urothelial Hyperplasia of the Urinary Bladder.	The precursor nature of papillary urothelial hyperplasia of the urinary bladder is uncertain. In this study, we investigated the telomerase reverse transcriptase (TERT) promoter and fibroblast growth factor receptor 3 (FGFR3) mutations in 82 patients with papillary urothelial hyperplasia lesions. Thirty-eight patients presented with papillary urothelial hyperplasia and concurrent noninvasive papillary urothelial carcinoma, and 44 patients presented with de novo papillary urothelial hyperplasia. The prevalence of the TERT promoter and FGFR3 mutations is compared between de novo papillary urothelial hyperplasia and those with concurrent papillary urothelial carcinoma. Mutational concordance between papillary urothelial hyperplasia and concurrent carcinoma was also compared. The TERT promoter mutations were detected in 44% (36/82) of papillary urothelial hyperplasia, including 23 (23/38, 61%) papillary urothelial hyperplasia with urothelial carcinoma and 13 (13/44, 29%) de novo papillary urothelial hyperplasia. The overall concordance of TERT promoter mutation status between papillary urothelial hyperplasia and concurrent urothelial carcinoma was 76%. The overall FGFR3 mutation rate of papillary urothelial hyperplasia was 23% (19/82). FGFR3 mutations were detected in 11 patients with papillary urothelial hyperplasia and concurrent urothelial carcinoma (11/38, 29%) and 8 patients with de novo papillary urothelial hyperplasia (8/44, 18%). Identical FGFR3 mutation status was detected in both papillary urothelial hyperplasia and urothelial carcinoma components in all 11 patients with FGFR3 mutations. Our findings provide strong evidence of a genetic association between papillary urothelial hyperplasia and urothelial carcinoma. High frequency of TERT promoter and FGFR3 mutations suggests the precursor role of papillary urothelial hyperplasia in urothelial carcinogenesis.	bladder
Methylation analysis of histone 4-related gene HIST1H4F and its effect on gene expression in bladder cancer.	Recently, aberrant DNA methylation of the HIST1H4F gene (encodes Histone 4 protein) has been shown in many types of cancer, which may serve as a promising biomarker for early cancer diagnosis. However, the correlation between DNA methylation of the HIST1H4F gene and its role in gene expression is unclear in bladder cancer. Therefore, the first objective of this study is to explore the DNA methylation pattern of the HIST1H4F gene and then further elucidate its effects on HIST1H4F mRNA expression in bladder cancer. To this end, the methylation pattern of the HIST1H4F gene was analyzed by pyrosequencing and the effects of the methylation profiles of this gene on HIST1H4F mRNA expression in bladder cancer were examined by qRT-PCR. Sequencing analysis revealed significantly higher methylation frequencies of the HIST1H4F gene in bladder tumor samples compared to normal samples (p < 0,0001). However, when we evaluated the correlations between hypermethylation of HIST1H4F and the clinicopathological parameters (tumor stage, tumor grade, lymph node metastasis, muscle-invasion), no significant difference was found between the groups (p > 0.05). In addition, we examined the role of hypermethylation of the HIST1H4F gene on HIST1H4F mRNA expression. We found that hypermethylation of HIST1H4F in the exon have no effect HIST1H4F mRNA expression in bladder cancer (p > 0.05). We also confirmed our finding in cultured T24 cell line which HIST1H4F gene is hypermethylated. Our results suggest that hypermethylation of the HIST1H4F seems to be a promising early diagnostic biomarker in bladder cancer patients. However, further studies are needed to determine the role of HIST1H4F hypermethylation in tumorigenesis.	bladder
[Frailty and surgical tolerability in elderly patients undergoing robot-assisted radical cystectomy (RARC)].	Robot-assisted radical cystectomy (RARC) has become a gold standard therapeutic option for muscle-invasive bladder cancer and selected cases with T1 bladder cancer. Due to the rapid aging worldwide and the outstanding performance of the da Vinci surgical system, the surgical indication of RARC in elderly men is often a matter of controversy. In this manuscript, we investigated previous literature regarding the complication rates and frailty among elderly patients undergoing RARC for bladder cancer.	bladder
Systematic radiomics analysis based on multiparameter MRI to preoperatively predict the expression of Ki67 and histological grade in patients with bladder cancer.	OBJECTIVES: Bladder cancer is among the most prevalent urothelial malignancies. Radiomics-based preoperative prediction of Ki67 and histological grade will facilitate clinical decision-making. METHODS: This retrospective study recruited 283 bladder cancer patients between 2012 and 2021. Multiparameter MRI sequences included: T1WI, T2WI, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) imaging. The radiomics features of intratumoral and peritumoral regions were extracted simultaneously. Max-Relevance and Min-Redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) algorithms were employed to select the features. Six machine learning-based classifiers were adopted to construct the radiomics models, and the best was chosen for the model construction. RESULTS: The mRMR and LASSO algorithms were more suitable for Ki67 and histological grade, respectively. Additionally, Ki67 had a higher proportion of intratumoral features, while peritumoral features accounted for a greater proportion of the histological grade. Random forests performed the best in predicting both pathological outcomes. Consequently, the multiparameter MRI (MP-MRI) models achieved area under the curve (AUC) values of 0.977 and 0.852 for Ki67 in training and test sets, respectively, and 0.972 and 0.710 for the histological grade. CONCLUSION: Radiomics holds the potential to predict multiple pathological outcomes of bladder cancer preoperatively and are expected to provide clinical decision-making guidance. Furthermore, our work inspired the process of radiomics research. ADVANCES IN KNOWLEDGE: This study demonstrated that different feature selection techniques, segmentation regions, classifiers, and MRI sequences will affect the performance of the model. We systematically demonstrated that radiomics can predict histological grade and Ki67.	bladder
Disparities in cause-specific mortality by race and sex among bladder cancer patients from the SEER database.	PURPOSE: Previous literature shows that more bladder cancer patients overall die from causes other than the primary malignancy. Given known disparities in bladder cancer outcomes by race and sex, we aimed to characterize differences in cause-specific mortality for bladder cancer patients by these demographics. METHODS: We identified 215,252 bladder cancer patients diagnosed with bladder cancer from 2000 to 2017 in the SEER 18 database. We calculated cumulative incidence of death from seven causes (bladder cancer, COPD, diabetes, heart disease, external, other cancer, other) to assess differences in cause-specific mortality between race and sex subgroups. We used multivariable Cox proportional hazards regression and Fine-Gray competing risk models to compare risk of bladder cancer-specific mortality between race and sex subgroups overall and stratified by cancer stage. RESULTS: 17% of patients died from bladder cancer (n = 36,923), 30% died from other causes (n = 65,076), and 53% were alive (n = 113,253). Among those who died, the most common cause of death was bladder cancer, followed by other cancer and diseases of the heart. All race-sex subgroups were more likely than white men to die from bladder cancer. Compared to white men, white women (HR: 1.20, 95% CI: 1.17-1.23) and Black women (HR: 1.57, 95% CI: 1.49-1.66) had a higher risk of dying from bladder cancer, overall and stratified by stage. CONCLUSION: Among bladder cancer patients, death from other causes especially other cancer and heart disease contributed a large proportion of mortality. We found differences in cause-specific mortality by race-sex subgroups, with Black women having a particularly high risk of dying from bladder cancer.	bladder
Adenocarcinoma of the Bladder: Assessment of Survival Advantage Associated With Radical Cystectomy and Comparison With Urothelial Bladder Cancer.	PURPOSE: To evaluate the association between radical cystectomy (RC) and cancer-specific mortality (CSM) in patients diagnosed with adenocarcinoma of the bladder (ACB). Moreover, to directly compare the survival advantage of RC between ACB vs. urothelial bladder cancer (UBC). MATERIALS AND METHODS: Non-metastatic muscle-invasive ACB and UBC patients were identified within Surveillance, Epidemiology, and End Results database (SEER 2000-2018). All analyses were stratified between RC vs. no-RC, in either organ-confined (OC: T(2)N(0)M(0)) or non-organ-confined (NOC: T(3-4)N(0)M(0) or T(any)N(1-3)M(0)) stages. Propensity score matching (PSM), cumulative incidence plots, competing risks regression (CRR) analyses, and 3 months' landmark analyses were performed. RESULTS: Overall, 1,005 ACB and 47,741 UBC patients were identified, of whom 475 (47%) and 19,499 (41%) were treated with RC, respectively. After PSM, comparison between RC vs. no-RC applied to 127 vs. 127 OC-ACB, 7,611 vs. 7,611 OC-UBC, 143 vs. 143 NOC-ACB, and 4,664 vs. 4,664 NOC-UBC patients. 36-month CSM rates in RC vs. no-RC patients were 14 vs. 44% in OC-ACB, 18 vs. 39% in OC-UBC, 49 vs. 66% in NOC-ACB, and 44 vs. 56% in NOC-UBC patients. In CRR analyses, the effect of RC on CSM yielded a hazard ratio of 0.37 in OC-ACB, of 0.45 in OC-UBC, of 0.65 in NOC-ACB and of 0.68 in NOC-UBC patients (all P values<0.001). Landmark analyses virtually perfectly replicated the results. CONCLUSIONS: In ACB, regardless of stage, RC is associated with lower CSM. The magnitude of this survival advantage was greater in ACB than in UBC, even after control for immortal time bias.	bladder
EffectiveNess of a multimodal preHAbilitation program in patieNts with bladder canCEr undergoing radical cystectomy: protocol of the ENHANCE multicentre randomised controlled trial.	INTRODUCTION: Radical cystectomy (RC) is the standard treatment for patients with non-metastatic muscle-invasive bladder cancer, as well as for patients with therapy refractory high-risk non-muscle invasive bladder cancer. However, 50-65% of patients undergoing RC experience perioperative complications. The risk, severity and impact of these complications is associated with a patient's preoperative cardiorespiratory fitness, nutritional and smoking status and presence of anxiety and depression. There is emerging evidence supporting multimodal prehabilitation as a strategy to reduce the risk of complications and improve functional recovery after major cancer surgery. However, for bladder cancer the evidence is still limited. The aim of this study is to investigate the superiority of a multimodal prehabilitation programme versus standard-of-care in terms of reducing perioperative complications in patients with bladder cancer undergoing RC. METHODS AND ANALYSIS: This multicentre, open label, prospective, randomised controlled trial, will include 154 patients with bladder cancer undergoing RC. Patients are recruited from eight hospitals in The Netherlands and will be randomly (1:1) allocated to the intervention group receiving a structured multimodal prehabilitation programme of approximately 3-6 weeks, or to the control group receiving standard-of-care. The primary outcome is the proportion of patients who develop one or more grade ≥2 complications (according to the Clavien-Dindo classification) within 90 days of surgery. Secondary outcomes include cardiorespiratory fitness, length of hospital stay, health-related quality of life, tumour tissue biomarkers of hypoxia, immune cell infiltration and cost-effectiveness. Data collection will take place at baseline, before surgery and 4 and 12 weeks after surgery. ETHICS AND DISSEMINATION: Ethical approval for this study was granted by the Medical Ethics Committee NedMec (Amsterdam, The Netherlands) under reference number 22-595/NL78792.031.22. Results of the study will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05480735.	bladder
Efficacy of Combined Pembrolizumab and Pelvic Radiotherapy for Bladder Cancer With Rectal Metastases.	BACKGROUND/AIM: Rectal metastases from urothelial carcinoma (UC) are extremely rare with poor prognosis when treated with gemcitabine and cisplatin (GC) chemotherapy, radiation therapy, and total pelvic exenteration. Long-term survival has not been observed in patients treated with GC chemotherapy, radiation therapy, or total pelvic resection. However, there have been no reports on the efficacy of pembrolizumab therapy for this specific condition. Herein, we describe a case of rectal metastasis from UC, treated with combined pembrolizumab and pelvic radiotherapy. CASE REPORT: A 67-year-old male patient with an invasive bladder tumour underwent robot-assisted radical cystectomy and ileal conduit diversion followed by neoadjuvant GC chemotherapy. The pathological findings showed high-grade UC, pT4a, with a negative surgical margin. He presented with an impacted ileus due to severe rectal stenosis on postoperative day 35 and underwent a colostomy. Pathologically, rectal biopsy confirmed rectal metastasis; thus, the patient was started on pembrolizumab 200 mg every 3 weeks and pelvic radiotherapy with a total dose of 45 Gy. The rectal metastases remained well controlled with stable disease status, and no adverse events were observed 10 months after the initiation of combined pembrolizumab and pelvic radiotherapy. CONCLUSION: Pembrolizumab combined with radiation therapy may be an alternative treatment for rectal metastases from UC.	bladder
A new biomarker panel of ultraconserved long non-coding RNAs for bladder cancer prognosis by a machine learning based methodology.	BACKGROUND: Recent studies have indicated that a special class of long non-coding RNAs (lncRNAs), namely Transcribed-Ultraconservative Regions are transcribed from specific DNA regions (T-UCRs), 100[Formula: see text] conserved in human, mouse, and rat genomes. This is noticeable, as lncRNAs are usually poorly conserved. Despite their peculiarities, T-UCRs remain very understudied in many diseases, including cancer and, yet, it is known that dysregulation of T-UCRs is associated with cancer as well as with human neurological, cardiovascular, and developmental pathologies. We have recently reported the T-UCR uc.8+ as a potential prognostic biomarker in bladder cancer. RESULTS: The aim of this work is to develop a methodology, based on machine learning techniques, for the selection of a predictive signature panel for bladder cancer onset. To this end, we analyzed the expression profiles of T-UCRs from surgically removed normal and bladder cancer tissues, by using custom expression microarray. Bladder tissue samples from 24 bladder cancer patients (12 Low Grade and 12 High Grade), with complete clinical data, and 17 control samples from normal bladder epithelium were analysed. After the selection of preferentially expressed and statistically significant T-UCRs, we adopted an ensemble of statistical and machine learning based approaches (i.e., logistic regression, Random Forest, XGBoost and LASSO) for ranking the most important diagnostic molecules. We identified a signature panel of 13 selected T-UCRs with altered expression profiles in cancer, able to efficiently discriminate between normal and bladder cancer patient samples. Also, using this signature panel, we classified bladder cancer patients in four groups, each characterized by a different survival extent. As expected, the group including only Low Grade bladder cancer patients had greater overall survival than patients with the majority of High Grade bladder cancer. However, a specific signature of deregulated T-UCRs identifies sub-types of bladder cancer patients with different prognosis regardless of the bladder cancer Grade. CONCLUSIONS: Here we present the results for the classification of bladder cancer (Low and High Grade) patient samples and normal bladder epithelium controls by using a machine learning application. The T-UCR's panel can be used for learning an eXplainable Artificial Intelligent model and develop a robust decision support system for bladder cancer early diagnosis providing urinary T-UCRs data of new patients. The use of this system instead of the current methodology will result in a non-invasive approach, reducing uncomfortable procedures (such as cystoscopy) for the patients. Overall, these results raise the possibility of new automatic systems, which could help the RNA-based prognosis and/or the cancer therapy in bladder cancer patients, and demonstrate the successful application of Artificial Intelligence to the definition of an independent prognostic biomarker panel.	bladder
o-Toluidine metabolism and effects in the urinary bladder of humanized-liver mice.	Occupational exposure to aromatic amines is one of the most important risk factors for urinary bladder cancer. When considering the carcinogenesis of aromatic amines, metabolism of aromatic amines in the liver is an important factor. In the present study, we administered ortho-toluidine (OTD) in the diet to mice for 4 weeks. We used NOG-TKm30 mice (control) and humanized-liver mice, established via human hepatocyte transplantation, to compare differences in OTD-induced expression of metabolic enzymes in human and mouse liver cells. We also investigated OTD-urinary metabolites and proliferative effects on the urinary bladder epithelium. RNA and immunohistochemical analyses revealed that expression of N-acetyltransferases mRNA in the liver tended to be lower than that of the P450 enzymes, and that OTD administration had little effect on N-acetyltransferase mRNA expression levels. However, expression of CYP3A4 was increased in the livers of humanized-liver mice, and expression of Cyp2c29 (human CYP2C9/19) was increased in the livers of NOG-TKm30 mice. OTD metabolites in the urine and cell proliferation activities in the bladder urothelium of NOG-TKm30 and humanized-liver mice were similar. However, the concentration of OTD in the urine of NOG-TKm30 mice was markedly higher than in the urine of humanized-liver mice. These data demonstrate differences in hepatic metabolic enzyme expression induced by OTD in human and mouse liver cells, and consequent differences in the metabolism of OTD by human and mouse liver cells. This type of difference could have a profound impact on the carcinogenicity of compounds that are metabolized by the liver, and consequently, would be important in the extrapolation of data from animals to humans.	bladder